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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 1994 - March 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
december 1992
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-380-1
EC Name:
-
Cas Number:
133336-92-2
Molecular formula:
C29H28N4O2
IUPAC Name:
1-(4-methylphenyl)-3-{4-[(4-{[(4-methylphenyl)carbamoyl]amino}phenyl)methyl]phenyl}urea
Test material form:
solid: particulate/powder
Details on test material:
- Particle size distribution: 10%: < 23.94 µm
- Density: 1.32 g/cm3 (20°C)
- Test substance storage: at room temperature in the dark
- Stability under storage conditions: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: BRL Ltd., Basel, Switzerland.
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males 224 - 242 gram, females 171 - 188 gram).
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled polycarbonate cages.
- Diet: Free access to pelleted rodent diet (Kliba 343 from KlingentalmOhle AG, Kaiseraugst, Switzerland).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 February 1994 to 3 March 1994

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Remarks:
adjusted for specific gravity: 1.036
Details on oral exposure:
Frequency: single dosage, on Day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
Formulation (w/w) was prepared immediately prior to dosing. The test substance was prepared in vehicle and adjustment was made for specific gravity of vehicle. Homogeneity was obtained by the use of a mechanical stirrer and electric blender.
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
10 (5 males and 5 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

Frequency of observations and weighing:
- Mortality/Viability: Twice daily.
- Body weights: Days 1 (pre-administration), 8 and 15.
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: Yes, all animals
- Other examinations performed: none.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the study .
Clinical signs:
Clinical signs observed in all animals on day 1 only, included lethargy and uncoordinated movements. One male also showed hunched posture on day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
According to Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
In an acute oral toxicity study with KY-AF in rats, performed according to EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An assessment of acute oral toxicity with KY-AF in the rat was performed according to EC test guideline and in accordance with GLP principles. KY-AF was administired by oral gavage to 5 male and 5 female Wistar rats at 2000 mg/kg bw. No mortality occured. Lethargy and uncoordinated movements were observed in all animals on day 1 and one male also showed hunched posture. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of KY-AF in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, KY-AF does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

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